Alzheimer's disease (AD) is a neurodegenerative disease of the brain characterized by dementia, cognitive impairment and memory loss. Formation and accumulation of aggregates of &-amyloid (AB) peptides in the brain are critical factors contributing to the development and progression of AD. Currently, early appraisal of clinical symptoms for diagnosis of AD is often difficult and unreliable. Therefore, there is an urgent need for in vivo imaging agents, which can specifically demonstrate the location and density of amyloid plaques in the brain. The objective of this project is to develop potential 1-123 labeled diagnostic imaging agents specific for detection of AB plaques. Recent advances in developing tracers for binding A13 plaques suggest that there are specific and saturable binding sites on the aggregates of At3 that can be selectively labeled and imaged in vivo. The proposed agents are derivatives of stilbenes containing a p-MezN-, -SH, -SMe, -0Me or -OH group on one of the benzene rings, while radioactive iodine can be attached to the other benzene ring without affecting the binding affinity. They are simple, relatively small, neutral and lipophilic. On the basis of their exquisitely high binding affinity to At3140 aggregates (Ki at the range of 0.1-40 nM), they are suitable candidates as A&-plaque-selective imaging agents. They also showed ability to penetrate the intact blood-brain barrier, an essential pre-requisite for a useful plaque-imaging agent. The proposed synthesis and methodology provide a framework to test the hypothesis that small probes can be used to detect At3 plaques in vivo. The proposed compounds are innovative and carefully crafted to meet the stringent requirements for t3-amyloid imaging agents. Together with the compelling preliminary data presented in this project we believe that At3 plaque-selective imaging agents can be successfully developed. The At3-plaque-specific imaging agents will be useful for early detection or monitoring the progression and effectiveness of treatment of AD.